DE3134728A1 - Material for bone implants, process for its production and use - Google Patents

Abstract

Tricalcium phosphate ceramic with a degree of porosity of more than 50% is impregnated with a broad-spectrum microbicide and coated with a tissue-compatible, slowly biodegradable coating. The material is suitable for bone implants and coatings of endoprostheses which can be heavily loaded.

Description

The present invention is a material for

Implants, which are used for a wide variety of purposes can and is characterized by excellent long-term tolerance and long-lasting protection against primary and secondary infections.

As a material for bone implants in particular the completely inert metals, highly annealed aluminum oxides, but also plastics such as polymethyl methacrylate and polymethyl methacrylate-methyl acrylate copolymers have proven successful. Especially these organic Polymers can be and have been successfully impregnated with broad spectrum microbicides has proven itself in practice; see Wahlig and Buchholz, Chirurg 43, p. 441 - 445 (1972).

Sintered hydroxylappatites have also received special attention recently or Tricalciumphosphate obtained, depending on the degree of their macroporosity and Microporosity grows more or less well with the bone substance or even be reabsorbed by the bone; see.

Peelen, Rejda and de Groot, Ceramurgia International, Vol. 4, N. 2, 1978, page 71 and de Groot, Biomaterials 1980, Vol. 1, page 47. With increasing Porosity also increases the degradability of this material, but decreases in the same Measure the mechanical stability.

It has also been proposed to be made from a matrix material absorbable sintered calcium phosphates, which are made from calcium oxide and P205 in one Amount ratio of 5: 1 to 2: 1 and an antibiotic to establish a depot of controlled drug delivery kinetics. For practical application became further proposed the powder obtained in this way with auxiliaries to be coated or microencapsulated. However, these materials do not yet have any Found its way into the practice.

A major disadvantage of all previous materials for bone implants is that a relatively high percentage sooner or later lead to infections which can mostly even be addressed as failure of the implantation.

Impregnation of bone implant materials with broad spectrum microbicides, especially with suitable antibiotics, only leads to for a certain time Success, because afterwards the existing and released quantities of the active ingredient are so strong sink so that they can no longer have any effect. Residual foci of infection or Subsequent secondary infections via the bloodstream can then occur at the seams between implant and bone lead to infection and inflammation, mostly completely question the success of the implantation. Even when using ball chains organic polymers, which contain significant amounts of antibiotics, must have them surgically removed after some time, which involves a not inconsiderable risk associated with complication and reinfection.

In the patent application P 31 06 445 is a method for production proposed a tricalcium phosphate bone ceramic for use in a bone implant in which the ceramic starting material is hydrogen peroxide before the firing process to form a ceramic with a defined pore size is added and after A disinfectant or antibiotic is applied to the firing process and added to the All to achieve a delayed release with a polymer of certain layer thicknesses is covered. Polydextran in particular is mentioned as a polymer. It has shown, that polydextran coatings are tissue-compatible and biodegradable, however, it is still too quickly resolved for practice, in the German patent application P 31 10 681 a material for bone implants has been proposed which in particular from polymethyl acrylate, polymethyl methacrylate-methyl acrylate copolymers or tricalcium phosphate ceramic with microporous and macroporous structure, which is optionally impregnated with a broad spectrum microbicide, which in addition contains a silver compound. In the manufacture of tricalcium phosphate ceramics with microporous and macroporous structure, the tricalcium phosphate powder is preferable by adding water or 1 to 3 show aqueous hydrogen peroxide solutions granulated on a plate granulator. The granules obtained in this way provide evidence the firing process has a porosity of about 60% or more.

The invention has set itself the task of long-term tolerance of bone implants and improve the likelihood of earlier or Significantly prevent later complications. She has continued set the task of exploring the possible uses of previously known materials widen and optimize their properties. Still has the invention has set itself the task of providing a material available, which in osteomyelitic bone cavities or third qradiq open fractures for Prophylaxis of osteomyelitis can be introduced.

This object is achieved by a material for bone implants made of tricalcium phosphate ceramic with microporous and macroporous structure, which is impregnated with at least one broad-spectrum microbicide, which is characterized by is that the tricalcium phosphate ceramic has a degree of porosity of more than 50% and covered with a commercially compatible, slowly biodegradable coating is.

High-melting fats are particularly suitable as coating materials, Polyglycolic acids, polyglycolic acid-lactic acid copolymers, alkylated cellulose derivatives, such as ethyl cellulose and methyl cellulose or high molecular starches.

While deforming the tricalcium phosphate powder with water and hydrogen peroxide in the slip sweetening process porosities up to a maximum of 50% tricalcium phosphate ceramics are produced from the same material during granulation with porosities of more than 50%.

60% porosity is obtained even without the addition of H202.

By adding H 2 O 2, this porosity can easily be increased to 65, 70 or 75% can be increased. The plate granulation process has proven particularly successful, at the same time applied to the powder and water on a rotating plate will. Firing takes place at temperatures of 950 - 1,400 C, preferably at 1.100 to 1.2500 C.

Optimal results are achieved at 1.1800 C, with 6 hours.

The heating-up time and 24 hours cooling down must be observed.

All active ingredients that are sufficient can be used as broad spectrum microbicides are effective, durable and resorbable by a porous tricuminium phosphate ceramic, for example PVP iodine (Betaisodona t hosphomycin (wosfocin Flucloxacillin (Staphylex ), Aminoqlycoside (Certomycin The antibiotic or microbicide one becomes dependent choose from the respective resistance situation. If the pathogen in question is already is recognized and checked for resistance, one becomes effective against this pathogen Select antibiotic. If the germs are very resistant, you will definitely be one Apply a broad spectrum microbicide such as PVP iodine. In osteomyelitis is the main causative agent Stapylococcus aureus, of which there are already several resistant strains.

It has thus been shown that a tricalcium phosphate ceramic with a porosity of over 50% and a tissue-compatible, biologically slower degradable coating is suitable, the long-term tolerance of bone implants to improve. It is therefore not absolutely necessary to add a silver compound to the material to be added, provided that the above conditions are met.

The material according to the invention is excellently suited for bone implants in infected and non-infected bones. In addition, it can also be used for this conventional and mechanically very hard-wearing endoprostheses with to cover the material according to the invention firmly and thereby the high mechanical Stability of a metal core with the good long-term compatibility of the invention Combine materials.

In the treatment of osteomyelitic bone cavities or third degree Open fractures surgically becomes everything cleared out necrotic material and then introduced a seal made of the material according to the invention. This seal Firstly leads to the healing of the infection, with a locally high antibiotic level is achieved.

Second, the ceramic also serves as a bone substitute material, which is converted into the newly formed bone. Another operation, e.g. Legs Cancellous plastic surgery is not required. In the animal experiment, the ceramic material was completely resorbed after 8-10 weeks and replaced by bone.

Preferred embodiments are shown in the following examples explained in more detail.

Example 1 Commercially available tricalcium phosphate (order no. 2143 Merck) with a grain size of about 1 to 2 ß is by adding water or 1 to 3 % aqueous hydrogen peroxide solutions granulated on a plate granulator. The plate granulator used had a plate diameter of 35 cm, a The edge of the plate is 7 cm, the axis is inclined at 45 °, and the speed of rotation 45 revolutions per minute and a material throughput of approx.

2 kg per hour. The liquid addition is approx. 30% by weight of the powder material. About 500 q of the powder are stirred beforehand through a Provide the shaking funnel with about twice the amount of liquid, with the liquid is applied via a spray gun. After a few minutes it forms the first usable granulate. It then continues to powder and liquid applied and granules removed continuously. Unless a smaller one Granules are desired, the granules can be of any size with a spoon the end can be removed from the flowing process. When using water at room temperature a granulate is obtained with a porosity of about 60%. By adding H202 the porosity is increased. The granules obtained in this way are stable enough to pass through Seven to be separated into fractions of different sizes. Too fine-grained granules can be fed back into the granulation process. Too large grain sizes can after appropriate comminution can be returned to the granulation process.

The finished granules are then burned. Here are Temperatures from 950 to 1,400 ° C are suitable. The best results are obtained if the granules are burned at about 1,180 ° C for one hour. It is heated for 6 hours and cools down for 24 hours. Such granules are mechanically strong enough to well absorbable and suitable, sufficient amounts of a microbicide or antibiotic to record.

The granulate obtained in this way is mixed with a solution in an eddy current process sprayed with PVP iodine and dried with warm air (approx. 500 C). With a porosity A content of dry antibiotic substance of up to 30% of the starting ceramic weight can range from approx. 50% can be achieved. Similar results are obtained with other antibiotics, such as phosphonycine, Flucloxacillin and the aminoglycoxide Certomycln achieved.

A granulate impregnated with an antibiotic is dragged along with it Polyglocolic acid dissolved in hexafluoroacetone or hexafluoroisopropanol, with q if necessary A little more cresol is added and heated to at least 550 ° C. Spraying the solution with air preheated to 80 - 900 C on the granulate. Polyglycolic acid precipitates as a coating as a result of cooling and evaporation of the solvent.

The granulated and impregnated granules thus obtained are for easy to handle for the surgeon. The antibiotic chosen is the one which appears optimal due to the previously tested resistance situation. Because of the The resorbability of the ceramic material does not have to be removed again later will. It exhibits immediate, medium-term, and long-term anti-infectious properties on. It is also suitable for fractions that are open to two or three degrees Support osteosynthesis by applying these granules and facing impending Protect infections and post-traumatic osteomyelitis. It is not a secondary intervention required and it is not necessary to use the body's own bone material in another location refer to.

Example 2 A granulate impregnated with an antibiotic according to Example 1 is coated with hot, high-melting fat (Dynasan 118 der Dynamit Nobel) with a melting point between 69 and 710 C. This fat is heated to 800 C. heated and air-free sprayed onto the granulate with a spray gun at close range, a nozzle with a passage of 0.6 mm has proven particularly useful. It will continuously sprayed so that the grease is always freshly sprayed on the surface of the granulate, otherwise a certain amount of abrasion and dust formation will occur can.

The material according to Example 1 and Example 2 has operated on dogs led to excellent results.

The use of seals has also proven particularly useful, the were made from a mixture of several sugar-coated granules. Due Different thickness of the coating obviously makes the active ingredient even more uniform released, so that a sufficient effective level of the Active ingredient is maintained.

Claims (6)

Material for bone implants, process for its manufacture and Its use P a t e n t a n s p r ü c h e 1. Material for bone implants made of tricalcium phosphate ceramic with microporous and macroporous structure, which is impregnated with at least one broad spectrum microbicide, characterized in that that the tricalcium phosphate ceramic has a degree of porosity of more than 50% and with at least one tissue-compatible, slowly biodegradable coating is covered. 2. Material according to claim 1, characterized in that the coating consists of at least one material from the group of high-melting fats, Polyglycolic acids, polyglycolic acid-lactic acid copolymers, alkylated cellulose derivatives or high molecular starches. 3. Process for the production of a material for bone implants made of tricalcium phosphate ceramic with microporous and macroporous structure, which is impregnated with at least one broad spectrum microbicide, characterized in that that one tricalcium phosphate powder with water and optionally additives for control the microporosity and macroporosity granulates 0 and at temperatures between 950 and 1400 C, preferably around 1.1800 C, burns after cooling with at least a microbicide soaked and then with at least one coating of a Tissue-compatible, slowly biodegradable material. 4. The method according to claim 3, characterized in that the coating material at least one substance from the group of high-melting fats, polyglycolic acids, Polyglycolic acid-lactic acid copolymers or alkylated cellulose derivatives or high molecular weight Contains starches. 5. The method according to claims 3 or 4, characterized in that as an additive to control the microporosity and macroporosity hydrogen peroxide is used. 6. Use of a material according to claims 1 or 2 as a coating on heavy-duty endoprostheses.